Planned Cesarean or planned vaginal delivery for twins: secondary analysis of randomized controlled trial.

OBJECTIVE: To evaluate whether there is a differential benefit of planned Cesarean delivery (CD) over planned vaginal delivery (VD) in women with a twin pregnancy and the first twin in cephalic presentation, depending on prespecified baseline maternal and pregnancy characteristics, and/or gestational age (GA) at delivery. METHODS: This was a secondary analysis of the Twin Birth Study, which included 2804 women with a twin pregnancy and the first twin (Twin A) in cephalic presentation between 32 + 0 and 38 + 6 weeks' gestation at 106 centers in 25 countries. Women were assigned randomly to either planned CD or planned VD. The main outcome measure was composite adverse perinatal outcome, defined as the occurrence of perinatal mortality or serious neonatal morbidity in at least one twin. The baseline maternal and pregnancy characteristics (markers) considered were maternal age, parity, history of CD, use of antenatal corticosteroids, estimated fetal weight (EFW) of Twin A, EFW of Twin B, > 25% difference in EFW between the twins, presentation of Twin B, chorionicity on ultrasound, method of conception, complications of pregnancy, ruptured membranes at randomization and GA at randomization. Separate logistic regression models were developed for each marker in order to model composite adverse perinatal outcome as a function of the specific marker, planned delivery mode and the interaction between these two terms. In addition, multivariable logistic regression analysis with backward variable elimination was performed separately in each arm of the trial. The association between planned mode of delivery and composite adverse perinatal outcome, according to GA at delivery, was assessed using logistic regression analysis. RESULTS: Of the 2804 women initially randomized, 1391 were included in each study arm. None of the studied baseline markers was associated with a differential benefit of planned CD over planned VD in the rate of composite adverse perinatal outcome. GA at delivery was associated differentially with composite adverse perinatal outcome in the treatment arms (P for interaction < 0.001). Among pregnancies delivered at 32 + 0 to 36 + 6 weeks, there was a trend towards a lower rate of composite adverse perinatal outcome in those in the planned-VD group compared with those in planned-CD group (29 (2.2%) vs 48 (3.6%) cases; odds ratio (OR) 0.62 (95% CI, 0.37-1.03)). In pregnancies delivered at or after 37 + 0 weeks, planned VD was associated with a significantly higher rate of composite adverse perinatal outcome, as compared with planned CD (23 (1.5%) vs 10 (0.7%) cases; OR, 2.25 (95% CI, 1.06-4.77)). CONCLUSION: The perinatal outcome of twin pregnancies with the first twin in cephalic presentation may differ depending on GA at delivery and planned mode of delivery. At 32-37 weeks, planned VD seems to be favorable, while, from around 37 weeks onwards, planned CD might be safer. The absolute risks of adverse perinatal outcomes at term are low and must be weighed against the increased maternal risks associated with planned CD. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Cesarean delivery or induction of labor in pre-labor twin gestations: a secondary analysis of the twin birth study.

BACKGROUND: In the Twin Birth Study, women at 320/7-386/7 weeks of gestation, in whom the first twin was in cephalic presentation, were randomized to planned vaginal delivery or cesarean section. The study found no significant differences in neonatal or maternal outcomes in the two planned mode of delivery groups. We aimed to compare neonatal and maternal outcomes of twin gestations without spontaneous onset of labor, who underwent induction of labor or pre-labor cesarean section as the intervention of induction may affect outcomes. METHODS: In this secondary analysis of the Twin Birth Study we compared those who had an induction of labor with those who had a pre-labor cesarean section. The primary outcome was a composite of fetal or neonatal death or serious neonatal morbidity. Secondary outcome was a composite of maternal morbidity and mortality. TRIAL REGISTRATION: NCT00187369. RESULTS: Of the 2804 women included in the Twin Birth Study, a total of 1347 (48%) women required a delivery before a spontaneous onset of labor occurred: 568 (42%) in the planned vaginal delivery arm and 779 (58%) in the planned cesarean arm. Induction of labor was attempted in 409 (30%), and 938 (70%) had a pre-labor cesarean section. The rate of intrapartum cesarean section in the induction of labor group was 41.3%. The rate of the primary outcome was comparable between the pre-labor cesarean section group and induction of labor group (1.65% vs. 1.97%; p = 0.61; OR 0.83; 95% CI 0.43-1.62). The maternal composite outcome was found to be lower with pre-labor cesarean section compared to induction of labor (7.25% vs. 11.25%; p = 0.01; OR 0.61; 95% CI 0.41-0.91). CONCLUSION: In women with twin gestation between 320/7-386/7 weeks of gestation, induction of labor and pre-labor cesarean section have similar neonatal outcomes. Pre-labor cesarean section is associated with favorable maternal outcomes which differs from the overall Twin Birth Study results. These data may be used to better counsel women with twin gestation who are faced with the decision of interventional delivery.

Urinary stress incontinence and other maternal outcomes 2 years after caesarean or vaginal birth for twin pregnancy: a multicentre randomised trial.

OBJECTIVE: Does planned caesarean compared with planned vaginal birth lower the risk of problematic urinary stress, faecal, or flatal incontinence? DESIGN: Women between 320/7 and 386/7 weeks of gestation with a twin pregnancy were randomised to planned caesarean or planned vaginal birth. SETTING: The trial took place at 106 centres in 25 countries. POPULATION: A total of 2305 of the 2804 women enrolled in the study completed questionnaires at 2 years (82.2% follow-up): 1155 in the planned caesarean group and 1150 in the planned vaginal birth group. METHODS: A structured self-administered questionnaire completed at 2 years postpartum. MAIN OUTCOME MEASURES: The primary maternal outcome of the Twin Birth Study was problematic urinary stress, or fecal, or flatal incontinence at 2 years RESULTS: Women in the planned caesarean group had lower problematic urinary stress incontinence rates compared with women in the planned vaginal birth group [93/1147 (8.11%) versus 140/1143 (12.25%); odds ratio, 0.63; 95% confidence interval, 0.47-0.83; P = 0.001]. Among those with problematic urinary stress incontinence, quality of life (measured using the Incontinence Impact Questionnaire, IIQ-7) was not different for planned caesarean versus planned vaginal birth groups [mean (SD): 18.4 (21.0) versus 19.1 (21.5); P = 0.82]. There were no differences in problematic faecal or flatal incontinence, or in other maternal outcomes. CONCLUSIONS: Among women with a twin pregnancy and no prior history of urinary stress incontinence, a management strategy of planned caesarean compared with planned vaginal birth reduces the risk of problematic urinary stress incontinence at 2 years postpartum. Our findings show that the prevalence but not the severity of urinary stress incontinence was associated with mode of birth. FUNDING: Canadian Institutes of Health Research (CIHR) (grant no. MCT-63164). TWEETABLE ABSTRACT: For women with twins, planned caesarean compared with planned vaginal birth is associated with decreased prevalence but not severity of urinary stress incontinence at 2 years.

Maternal outcomes at 3 months after planned caesarean section versus planned vaginal birth for twin pregnancies in the Twin Birth Study: a randomised controlled trial.

OBJECTIVE: To compare outcomes at 3 months post partum for women randomised to give birth by planned caesarean section (CS) or by planned vaginal birth (VB) in the Twin Birth Study (TBS). DESIGN: We invited women in the TBS to complete a 3-month follow-up questionnaire. SETTING: Two thousand and eight hundred and four women from 25 countries. POPULATION: Two thousand and five hundred and seventy women (92% response rate). METHODS: Women randomised between 13 December 2003 and 4 April 2011 in the TBS completed a questionnaire and outcomes were compared using an intention-to-treat approach. MAIN OUTCOME AND MEASURES: Breastfeeding, quality of life, depression, fatigue and urinary incontinence. RESULTS: We found no clinically important differences between groups in any outcome. In the planned CS versus planned VB groups, breastfeeding at any time after birth was reported by 84.4% versus 86.4% (P = 0.13); the mean physical and mental Short Form (36) Health Survey (SF-36) quality of life scores were 51.8 versus 51.6 (P = 0.65) and 46.7 versus 46.0 (P = 0.09), respectively; the mean Multidimensional Assessment of Fatigue score was 20.3 versus 20.8 (P = 0.14); the frequency of probable depression on the Edinburgh Postnatal Depression Scale was 14.0% versus 14.8% (P = 0.57); the rate of problematic urinary incontinence was 5.5% versus 6.4% (P = 0.31); and the mean Incontinence Impact Questionnaire-7 score was 20.5 versus 20.4 (P = 0.99). Partner relationships, including painful intercourse, were similar between the groups. CONCLUSION: For women with twin pregnancies randomised to planned CS compared with planned VB, outcomes at 3 months post partum did not differ. The mode of birth was not associated with problematic urinary incontinence or urinary incontinence that affected the quality of life. Contrary to previous studies, breastfeeding at 3 months was not increased with planned VB. TWEETABLE ABSTRACT: Planned mode of birth for twins doesn't affect maternal depression, wellbeing, incontinence or breastfeeding.

Maternal and infant predictors of attendance at Neonatal Follow-Up programmes.

BACKGROUND: Neonatal Follow-Up (NFU) programmes provide health services for families of infants at high risk of developmental problems following difficult or extremely premature birth: yet, up to 30% of families do not attend these programmes with their infants. METHODS: The study objective was to determine maternal and infant factors that predicted attendance at NFU programmes. Utilizing Andersen's Behavioural Model of Health Services Use, a prospective two-phase multi-site descriptive cohort study was conducted in three Canadian Neonatal Intensive Care Units (NICU) that refer to two affiliated NFU programmes. In Phase 1, 357 mothers completed standardized questionnaires that addressed maternal and infant factors, prior to their infants' NICU discharge. In Phase 2, attendance at NFU was followed at three time points over a 12-month period. Factors of interest included predisposing factors (e.g. demographic characteristics and social context); enabling factors (e.g. social support, travel distance, and income); and infant illness severity (i.e. needs factors). Multivariate logistic regression was used to estimate the odds ratio for each independent factor. RESULTS: Mothers parenting alone, experiencing higher levels of worry about maternal alcohol or drug use, or at greater distances from NFU were less likely to attend. Mothers experiencing higher maternal stress at the time of the infant's NICU hospitalization were more likely to attend NFU. No infant factors were predictive of NFU attendance. CONCLUSIONS: Mothers at risk of not attending NFU programmes with their infants require better identification, triage, referral and additional support to promote engagement with NFU programmes and improved quality of life for their high-risk infants.

Haemophilia prophylaxis: how can we justify the costs?

Severe haemophilia results in increased mortality and poorer quality of life. Factor prophylaxis leads to a more normal life, but is very costly; most of the cost is due to the high cost of replacement factor. Despite its high cost, factor prophylaxis has been adopted throughout the developed world--even in different health care systems. We argue that there are at least five possible reasons why societies may value factor prophylaxis despite its cost: (i) it is directed towards an inherited disease, (ii) the treatment is largely directed towards children, (iii) the disease is rare and the overall cost to society is small, (iv) the treatment is preventative, and v) the high cost is largely the result of providing safe products. In an era of rising health care costs, there is a strong research agenda to establish the factors that determine the value of expensive therapies for rare diseases like haemophilia.

The Early External Cephalic Version (ECV) 2 Trial: an international multicentre randomised controlled trial of timing of ECV for breech pregnancies.

OBJECTIVE: To investigate whether initiating external cephalic version (ECV) earlier in pregnancy might increase the rate of successful ECV procedures, and be more effective in decreasing the rate of non-cephalic presentation at birth and of caesarean section. DESIGN: An unblinded multicentred randomised controlled trial. SETTING: A total of 1543 women were randomised from 68 centres in 21 countries. POPULATION: Women with a singleton breech fetus at a gestational age of 33(0/7) weeks (231 days) to 35(6/7) weeks (251 days) of gestation were included. METHODS: Participants were randomly assigned to having a first ECV procedure between the gestational ages of 34(0/7) (238 days) and 35(6/7) weeks of gestation (early ECV group) or at or after 37(0/7) (259 days) weeks of gestation (delayed ECV group). MAIN OUTCOME MEASURES: The primary outcome was the rate of caesarean section; the secondary outcome was the rate of preterm birth. RESULTS: Fewer fetuses were in a non-cephalic presentation at birth in the early ECV group (314/765 [41.1%] versus 377/768 [49.1%] in the delayed ECV group; relative risk [RR] 0.84, 95% CI 0.75, 0.94, P=0.002). There were no differences in rates of caesarean section (398/765 [52.0%] versus 430/768 [56.0%]; RR 0.93, 95% CI 0.85, 1.02, P=0.12) or in risk of preterm birth (50/765 [6.5%] versus 34/768 [4.4%]; RR 1.48, 95% CI 0.97, 2.26, P=0.07) between groups. CONCLUSION: External cephalic version at 34-35 weeks versus 37 or more weeks of gestation increases the likelihood of cephalic presentation at birth but does not reduce the rate of caesarean section and may increase the rate of preterm birth.

Recommendations for reporting economic evaluations of haemophilia prophylaxis: a nominal groups consensus statement on behalf of the Economics Expert Working Group of The International Prophylaxis Study Group.

BACKGROUND: The need for clearly reported studies evaluating the cost of prophylaxis and its overall outcomes has been recommended from previous literature. OBJECTIVES: To establish minimal ''core standards'' that can be followed when conducting and reporting economic evaluations of hemophilia prophylaxis. METHODS: Ten members of the IPSG Economic Analysis Working Group participated in a consensus process using the Nominal Groups Technique (NGT). The following topics relating to the economic analysis of prophylaxis studies were addressed; Whose perspective should be taken? Which is the best methodological approach? Is micro- or macro-costing the best costing strategy? What information must be presented about costs and outcomes in order to facilitate local and international interpretation? RESULTS: The group suggests studies on the economic impact of prophylaxis should be viewed from a societal perspective and be reported using a Cost Utility Analysis (CUA) (with consideration of also reporting Cost Benefit Analysis [CBA]). All costs that exceed $500 should be used to measure the costs of prophylaxis (macro strategy) including items such as clotting factor costs, hospitalizations, surgical procedures, productivity loss and number of days lost from school or work. Generic and disease specific quality of lífe and utility measures should be used to report the outcomes of the study. CONCLUSIONS: The IPSG has suggested minimal core standards to be applied to the reporting of economic evaluations of hemophilia prophylaxis. Standardized reporting will facilitate the comparison of studies and will allow for more rational policy decisions and treatment choices.

The Control of Hypertension In Pregnancy Study pilot trial.

OBJECTIVE: To determine whether 'less tight' (versus 'tight') control of nonsevere hypertension results in a difference in diastolic blood pressure (dBP) between groups. DESIGN: Randomised controlled trial (ISRCTN#57277508). SETTING: Seventeen obstetric centres in Canada, Australia, New Zealand, and UK. POPULATION: Inclusion: pregnant women, dBP 90-109 mmHg, pre-existing/gestational hypertension; live fetus(es); and 20-33(+6) weeks. Exclusion: systolic blood pressure > or = 170 mmHg and proteinuria, contraindication, or major fetal anomaly. METHODS: Randomisation to less tight (target dBP, 100 mmHg) or tight (target dBP, 85 mmHg) blood pressure control. MAIN OUTCOME MEASURES: Primary: mean dBP at 28, 32 and 36 weeks. Secondary: clinician compliance and women's satisfaction. Other: serious perinatal and maternal complications. RESULTS: A total of 132 women were randomised to less tight (n = 66; seven had no study visit) or tight control (n= 66; one was lost to follow up; seven had no study visit). Mean dBP was significantly lower with tight control: -3.5 mmHg, 95% credible interval (-6.4, -0.6). Clinician compliance was 79% in both groups. Women were satisfied with their care. With less tight (versus tight) control, the rates of other treatments and outcomes were the following: post-randomisation antenatal antihypertensive medication use: 46 (69.7%) versus 58 (89.2%), severe hypertension: 38 (57.6%) versus 26 (40.0%), proteinuria: 16 (24.2%) versus 20 (30.8%), serious maternal complications: 3 (4.6%) versus 2 (3.1%), preterm birth: 24 (36.4%) versus 26 (40.0%), birthweight: 2675 +/- 858 versus 2501 +/- 855 g, neonatal intensive care unit (NICU) admission: 15 (22.7%) versus 22 (34.4%), and serious perinatal complications: 9 (13.6%) versus 14 (21.5%). CONCLUSION: The CHIPS pilot trial confirms the feasibility and importance of a large definitive trial to determine the effects of less tight control on serious perinatal and maternal complications.

Women's views of their experiences in the CHIPS (Control of Hypertension in Pregnancy Study) Pilot Trial.

BACKGROUND: Satisfaction with maternity care is strongly related to the patient-caregiver relationship and involvement in the decision-making process. We sought to compare women's views about their care in a randomized trial of 'less tight' vs. 'tight' control of non-proteinuric pre-existing or gestational hypertension in pregnancy. METHODS: In the CHIPS Pilot Trial, women completed a postpartum questionnaire to assess their likes and dislikes about their blood pressure (BP) management and trial participation. Comparisons were descriptive. RESULTS: Baseline information was similar for the 'less tight' and 'tight' control groups. Of 132 women, 126 (95.5%) from 17 centers completed a postpartum questionnaire, usually within days of delivery. At least 90% of women in both groups were satisfied with their care, and would be willing to participate again or recommend participation to a friend. Women in both the 'less tight' and 'tight' groups were satisfied with BP management (98.4% vs. 95.1%), and the frequency of tests of maternal and fetal well being. Half of women in both groups perceived that their BP was too high and that caregivers thought that their BP was too high. More women in the 'less tight' (vs. the 'tight') control group took less medication than expected (71.7% vs. 38.2%). More women in the 'tight' (vs. the 'less tight') group took more medication than they expected (60.0% vs. 22.2%). At least 60% of all women used home BP monitoring. CONCLUSION: In the CHIPS Pilot Trial, while women stated that they were satisfied with their BP management and care, a surprising 50% in both groups thought that their BP was too high. The majority of women used home BP monitoring, the role of which must be further defined in hypertensive pregnancies.

Superiority of granisetron to dexamethasone plus prochlorperazine in the prevention of chemotherapy-induced emesis.

Trials of selective 5-hydroxytryptamine3 receptor antagonists have shown excellent antiemetic activity for chemotherapy containing cisplatin when compared with high-dose metoclopramide. There is little information about the efficacy of these new agents for chemotherapy other than for high-dose cisplatin. We performed a double-blind, randomized trial comparing a single dose of the 5-hydroxytryptamine3 receptor antagonist granisetron (BRL 43694A) as a single intravenous dose with dexamethasone plus prochlorperazine in 152 patients receiving their first course of moderately emetogenic chemotherapy (mainly doxorubicin- and cyclophosphamide-containing combinations). During the first 24 hours, there was a statistically significant advantage for the granisetron group in terms of the prevention of both nausea and emesis. There was no difference in the frequency of reported adverse events. We conclude that granisetron is more effective than dexamethasone plus prochlorperazine in patients who are receiving moderately emetogenic cytotoxic agents.

Randomized clinical trial of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer: an update. Ontario Clinical Oncology Group.

BACKGROUND: Breast-conservation surgery is now commonly used to treat breast cancer. Postoperative breast irradiation reduces cancer recurrence in the breast. There is still controversy concerning the necessity of irradiation of the breast in all patients. PURPOSE: We present an update of results from a randomized clinical trial designed to examine the efficacy of breast irradiation following conservation surgery in the treatment of women with axillary lymph node-negative breast cancer. The patients were enrolled from April 1984 through February 1989. Initial results were published in 1992 after a median follow-up time of 43 months. It was reported that recurrence of cancer in the breast occurred in 5.5% of the patients who received breast irradiation compared with 25.7% of those who did not. No difference in survival was detected between the two treatment groups. Now that the median patient follow-up has reached 7.6 years, the trial end points have been re-examined and an attempt has again been made to identify a group of patients at low risk for recurrence of cancer in the breast. METHODS: Eight hundred thirty-seven patients with node-negative breast cancer were randomly assigned to receive either radiation therapy (n = 416) or no radiation therapy (n = 421) following lumpectomy and axillary lymph node dissection. The cumulative local recurrence rate as a first event, distant recurrence (i.e., occurrence of metastasis) rate, and overall mortality rate for the treatment groups were described by the Kaplan-Meier method and compared with the use of the logrank test. The Cox proportional hazards model was used to adjust the observed treatment effect for the influence of various prognostic factors (patient age, tumor size, estrogen receptor level, and tumor histology) at study entry on the outcomes of local breast recurrence, distant recurrence, and overall mortality. All P values resulted from the use of two-tailed statistical tests. RESULTS: One hundred forty eight (35%) of the nonirradiated patients and 47 (11%) of the irradiated patients developed recurrent cancer in the breast (relative risk for patients in the former versus the latter group = 4.0; 95% confidence interval = 2.83-5.65; P < .0001). Ninety-nine (24%) of the patients in the former group have died compared with 87 (21%) in the latter group. Age (< 50 years), tumor size (> 2 cm), and tumor nuclear grade (poor) continued to be important predictors for local breast relapse. On the basis of these factors, we were unable to identify a subgroup of patients with a very low risk for local breast cancer recurrence. Tumor nuclear grade, as previously reported, and tumor size were important predictors for mortality. CONCLUSIONS: Breast irradiation was shown to reduce cancer recurrence in the breast, but there was no statistically significant reduction in mortality. A subgroup of patients with a very low risk for local breast recurrence who might not require radiation therapy was not identified.

Cost-effectiveness of the implantable cardioverter-defibrillator: results from the Canadian Implantable Defibrillator Study (CIDS).

BACKGROUND: In the Canadian Implantable Defibrillator Study (CIDS), we assessed the cost-effectiveness of the implantable cardioverter-defibrillator (ICD) in reducing the risk of death in survivors of previous ventricular tachycardia (VT) or fibrillation (VF). METHODS AND RESULTS: Healthcare resource use was collected prospectively on the first 430 patients enrolled in CIDS (n=212 ICD, n=218 amiodarone). Mean cost per patient, adjusted for censoring, was computed for each group based on initial therapy assignment. Incremental cost-effectiveness of ICD therapy was computed as the ratio of the difference in cost (ICD minus amiodarone) to the difference in life expectancy (both discounted at 3% per year). All costs are in 1999 Canadian dollars (C$1 approximately US$0.65). Over 6.3 years, mean cost per patient in the ICD group was C$87 715 versus C$38 600 in the amiodarone group (difference C$49 115; 95% CI C$25 502 to C$69 508). Life expectancy for the ICD group was 4.58 years versus 4.35 years for amiodarone (difference 0.23, 95% CI -0.09 to 0.55), for incremental cost-effectiveness of ICD therapy of C$213 543 per life-year gained. ICD benefit was greater in patients with low left ventricular ejection fraction (<35%), and cost-effectiveness in this group was more attractive (C$108 484). Alternative extrapolations of survival benefit and costs to 12 years indicated cost-effectiveness in the range of C$100 000 to C$150 000 per life-year gained. CONCLUSIONS: At C$213 543, the value for the money offered by ICD therapy is not attractive by currently accepted standards. Further research is warranted to identify the indications and patient subgroups for whom ICDs are a cost-effective use of resources.

Methodologic issues in trials of antiemetics.

Studies of antiemetics require consideration of methodologic issues that may not be of concern in trials of antineoplastics. This paper illustrates how the strength of the results of these studies can be affected by (1) the types of patients studied, (2) the sample size, (3) the trial design, (4) the choice and definition of outcome measures, and (5) the method of analysis.

Chemotherapy can prolong survival in patients with advanced non-small-cell lung cancer--report of a Canadian multicenter randomized trial.

The survival benefit of combination chemotherapy to patients with advanced non-small-cell carcinoma of the lung (NSCLC) is controversial. To study this question, the National Cancer Institute of Canada (NCIC) Clinical Trials Group conducted a prospective randomized trial comparing best supportive care (BSC) to two chemotherapy regimens, vindesine and cisplatin (VP), and cyclophosphamide, doxorubicin, and cisplatin (CAP). Between February 1983 and January 1986, 23 centers across Canada entered 251 patients on study. Eighteen centers participated in the three-arm schema (150 patients); centers choosing not to participate in a study with a no-chemotherapy arm followed a two-arm schema comparing VP with CAP (101 additional patients). Altogether, 233 patients were eligible. Patients had measurable or evaluable disease, with either distant metastases (82.5%) or bulky limited disease considered inoperable or unsuitable for radical radiotherapy. The treatment groups were comparable in terms of age, sex, performance status, histology, disease extent, and weight loss. The overall response rates (complete response [CR] plus partial response [PR]) on the chemotherapy arms were CAP, 15.3%, and VP, 25.3% (P = .06). Patients on the three-arm portion of the trial had a median survival of 32.6 weeks when treated with VP, 24.7 weeks with CAP, and 17 weeks with BSC. The significance of the differences in survival, adjusted for prognostic factors, is as follows: chemotherapy v BSC, P = .02; VP v BSC, P = .01; and CAP v BSC, P = .05. Toxicity on the chemotherapy arms was significant, with leukopenia of severe or greater degree occurring in 37.8% (CAP) and 40.0% (VP), severe vomiting in 12.2% (CAP) and 23.3% (VP), and severe neurotoxicity in 15.6% (VP).

Mastectomy or lumpectomy? Helping women make informed choices.

PURPOSE: To develop an instrument to help clinicians inform their patients about surgical treatment options for the treatment of breast cancer and to evaluate the impact of the instrument on the clinical encounter. METHODS: We developed an instrument, called the Decision Board, to present information regarding the benefits and risks of breast-conserving therapy (lumpectomy plus radiation therapy) and mastectomy to women with early-stage breast cancer to enable them to express a preference for the type of surgery. Seven surgeons from different communities in Ontario administered the instrument to women with newly diagnosed clinical stage I or II breast cancer over an 18-month period. Patients and surgeons were interviewed regarding acceptability of the instrument. The rates of breast-conserving surgery performed by surgeons before and after the introduction of the instrument were compared. RESULTS: The Decision Board was administered to 175 patients; 98% reported that the Decision Board was easy to understand, and 81% indicated that it helped them make a decision. The average score on a true/false test of comprehension was 11.8 of 14 (84%) (range, 6 to 14). Surgeons found the Decision Board to be helpful in presenting information to patients in 91% of consultations. The rate of breast-conserving surgery decreased when the Decision Board was introduced (88% v 73%, P =.001) CONCLUSION: The Decision Board is a simple method to improve communication and facilitate shared decision making. It was well accepted by patients and surgeons and easily applied in the community.

Economic evaluation of chemotherapy with mitoxantrone plus prednisone for symptomatic hormone-resistant prostate cancer: based on a Canadian randomized trial with palliative end points.

PURPOSE: To evaluate the economic consequences of the use of chemotherapy in patients with symptomatic hormone-resistant prostate cancer (HRPC) in the context of a previously published Canadian open-label, phase III, randomized trial with palliative end points. PATIENTS AND METHODS: The trial randomized 161 patients to initial treatment with mitoxantrone and prednisone (M + P) or to prednisone alone (P) and showed better palliation with M + P. There was no significant difference in survival. A detailed retrospective chart review was performed of resources used from randomization until death of 114 of 161 patients enrolled at the three largest centers: these included hospital admissions, outpatient visits, investigations, therapies (which included all chemotherapy and radiation), and palliative care. Cancer center and community hospital costs were calculated by using the hotel approximation method and case costing from the Ontario Case Cost Project, respectively. Cost-utility analysis was performed by transforming the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 global quality-of-life item measured every 3 weeks on trial to an estimate of utility, and extending the last known value through to death or last follow-up. RESULTS: The mean total cost until death or last follow-up by intention-to-treat was M + P CDN $27,300; P CDN $29,000. The 95% confidence intervals on the observed cost difference ranged from a saving of $9,200 for M + P (with palliative benefit) to an increased cost of $5,800 for M + P. The major proportion of cost (M + P 53% v P 66%; CDN $14,500 v $19,100) was for inpatient care. Initial M + P was consistently less expensive in whichever time period was used to compare costs. Cost-utility analysis showed M + P to be the preferred strategy with an upper 95% confidence interval for the incremental cost-utility ratio of CDN $19,700 per quality-adjusted life-year (QALY). CONCLUSION: A treatment that reduces symptoms and improves quality of life has the potential to reduce costs in other areas. Economic factors should not influence the clinical decision as to whether to use M + P in a symptomatic patient.

Improved survival in patients with poor-prognosis malignant melanoma treated with adjuvant levamisole: a phase III study by the National Cancer Institute of Canada Clinical Trials Group.

Five hundred forty-three patients with completely resected malignant melanoma who were considered to have a significant risk of developing recurrent disease were randomized to one of four study groups. One group received levamisole 2.5 mg/kg on 2 consecutive days weekly for 3 years, a second group received bacillus Calmette-Guérin (BCG) for 3 years. A third group alternated 8-week courses of BCG and levamisole for 3 years and a fourth group underwent clinical assessment at the same frequency as the three treatment groups. The median duration of follow-up is 8.5 years. The percentage of reduction in the death rate and the recurrence rate in the treatment groups compared with the control group was calculated using the Cox proportional hazards model and adjusted for age, sex, and stage as covariants. The patients treated with levamisole were estimated to have a 29% reduction in both the death rate (P = .08) and the recurrence rate (P = .09) compared with patients receiving no further treatment. Fifty-five patients discontinued levamisole early because of gastrointestinal intolerance or arthralgia, myalgia, fever, and immune leukopenia. The patients treated with BCG alternating with levamisole experienced a 10% reduction in the death rate and a 6% reduction in the recurrence rate, and the patients treated with BCG alone experienced a 4% reduction in the death rate and a 3% increase in the recurrence rate compared with the control group. The degree of improvement experienced by the patients that were treated by levamisole is of sufficient magnitude to warrant further investigation of this dose of levamisole as adjuvant treatment in patients with melanoma.

Effect of smoking cessation on mortality after myocardial infarction: meta-analysis of cohort studies.

OBJECTIVE: To determine the effect of smoking cessation on mortality after myocardial infarction. DATA SOURCES: English- and non-English-language articles published from 1966 through 1996 retrieved using keyword searches of MEDLINE and EMBASE supplemented by letters to authors and searching bibliographies of reviews. STUDY SELECTION: Selection of relevant abstracts and articles was performed by 2 independent reviewers. Articles were chosen that reported the results of cohort studies examining mortality in patients who quit vs continued smoking after myocardial infarction. DATA EXTRACTION: Mortality data were extracted from the selected articles by 2 independent reviewers. DATA SYNTHESIS: Twelve studies were included containing data on 5878 patients. The studies took place in 6 countries between 1949 and 1988. Duration of follow-up ranged from 2 to 10 years. All studies showed a mortality benefit associated with smoking cessation. The combined odds ratio based on a random effects model for death after myocardial infarction in those who quit smoking was 0.54 (95% confidence interval, 0.46-0.62). Relative risk reductions across studies ranged from 15% to 61%. The number needed to quit smoking to save 1 life is 13 assuming a mortality rate of 20% in continuing smokers. The mortality benefit was consistent regardless of sex, duration of follow-up, study site, and time period. CONCLUSION: Results of several cohort studies suggest that smoking cessation after myocardial infarction is associated with a significant decrease in mortality.

Economic evaluation of outpatient treatment with low-molecular-weight heparin for proximal vein thrombosis.

BACKGROUND: The safety and efficacy of taking low-molecular-weight heparin at home was previously demonstrated in a clinical trial in which patients with acute proximal deep vein thrombosis were randomized to receive either intravenous standard heparin in the hospital or subcutaneous low-molecular-weight heparin administered primarily at home. Treatment in the home has the potential to substantially reduce the cost to the health care system. METHODS: To conduct an economic evaluation we prospectively collected data on resource use and health-related quality of life (Medical Outcomes Study Short-Form 36) on the 300 patients who formed the trial stratum presenting with proximal vein thrombosis as outpatients, of whom 151 received standard heparin and 149 received low-molecular-weight heparin. The primary viewpoint of the analysis was societal, and costs included health care costs, patient travel costs, and productivity costs as a result of time off work. Costs were assessed over a period of 3 months from randomization. Quality of life was assessed as the change in Short-Form 36 domain scores from baseline to day 7 for each treatment group. All costs are reported in 1997 Canadian dollars. RESULTS: There were 11 recurrent thromboembolic events and 1 bleed in the 151 patients who received standard heparin; the corresponding data for the 149 patients receiving low-molecular-weight heparin were 10 and 4, respectively. The mean cost per patient who received standard heparin was Can $5323 compared with Can $2278 for low-molecular-weight heparin, a total societal cost savings per patient using low-molecular-weight heparin of Can $3045 (95% confidence interval, Can $2012-$4050). There was no difference in quality of life between the 2 groups except for the domain of social functioning, where a greater improvement from baseline to day 7 was observed for the low-molecular-weight heparin group vs the standard heparin group (P =.005). CONCLUSIONS: For patients with acute proximal deep vein thrombosis, treatment at home with low-molecular-weight heparin is less costly than hospital-based treatment with standard heparin. The economic evidence in favor of outpatient treatment with low-molecular-weight heparin exhibits dominance; a situation of reduced cost is created with no compromise in clinical outcomes or patients' quality of life.